Support is requested for a Keystone Symposia meeting entitled Enhancer Malfunction in Cancer, organized by Ali Shilatifard and Dale Dorsett. The meeting will be held in Santa Fe, New Mexico from January 21-25, 2016. Why point mutations in a general transcription factor are associated with specific forms of human malignancies has been a major question in cancer biology. Enhancers are DNA regulatory elements that can be transcribed and are key regulators of tissue-specific gene expression in development; their malfunction through point mutations in either regulatory elements or factors modulating enhancer-promoter communication could result in developmental problems. Indeed, recent genome-wide studies in the cataloging of somatic mutations in cancer have identified mutations in intergenic sequences encoding regulatory elements and in specific transcription factors that function in enhancer-promoter communication. This meeting will review recent reports in this regard and discuss the concept of enhancer malfunction in the misregulation of gene expression in disease pathogenesis, including cancer, and in development. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Noncoding RNAs in Health and Disease, which will share a keynote address and two plenary sessions with this meeting.